The edgewise interactions of anions with phenylalanine (Phe) aromatic rings in proteins, known as anion–quadrupole interactions, have been well studied. However, the anion–quadrupole interactions of the tyrosine (Tyr) and tryptophan (Trp) rings have been less well studied, probably because these have been considered weaker than interactions of anions hydrogen bonded to Trp/Tyr side chains. Distinguishing such hydrogen bonding interactions, we comprehensively surveyed the edgewise interactions of certain anions (aspartate, glutamate, and phosphate) with Trp, Tyr, and Phe rings in high-resolution, nonredundant protein single chains and interfaces (protein–protein, DNA/RNA–protein, and membrane–protein). Trp/Tyr anion–quadrupole interactions are common, with Trp showing the highest propensity and average interaction energy for this type of interaction. The energy of an anion–quadrupole interaction (−15.0 to 0.0 kcal/mol, based on quantum mechanical calculations) depends not only on the interaction geometry but also on the ring atom. The phosphate anions at DNA/RNA–protein interfaces interact with aromatic residues with energies comparable to that of aspartate/glutamate anion–quadrupole interactions. At DNA–protein interfaces, the frequency of aromatic ring participation in anion–quadrupole interactions is comparable to that of positive charge participation in salt bridges, suggesting an underappreciated role for anion–quadrupole interactions at DNA–protein (or membrane–protein) interfaces. Although less frequent than salt bridges in single-chain proteins, we observed highly conserved anion–quadrupole interactions in the structures of remote homologues, and evolutionary covariance-based residue contact score predictions suggest that conserved anion–quadrupole interacting pairs, like salt bridges, contribute to polypeptide folding, stability, and recognition.

中文翻译：

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蛋白质结构中阴离子-四极相互作用的综合分析

阴离子与蛋白质中苯丙氨酸（Phe）芳香环的边缘相互作用（称为阴离子-四极相互作用）已经得到了很好的研究。但是，对酪氨酸（Tyr）和色氨酸（Trp）环的阴离子-四极相互作用的研究较少，可能是因为它们被认为比与Trp / Tyr侧链键合的阴离子氢的相互作用弱。区分这种氢键相互作用，我们全面研究了某些阴离子（天冬氨酸，谷氨酸和磷酸根）与Trp，Tyr和Phe环在高分辨率，非冗余蛋白质单链和界面（蛋白质-蛋白质，DNA / RNA）中的边缘相互作用–蛋白和膜–蛋白）。Trp / Tyr阴离子-四极相互作用很常见，Trp显示了此类互动的最高倾向和平均互动能量。阴离子-四极相互作用的能量（−15.0至0.0 kcal / mol，基于量子力学计算）不仅取决于相互作用的几何形状，而且还取决于环原子。DNA / RNA-蛋白质界面上的磷酸根阴离子与芳族残基相互作用，其能量与天冬氨酸/谷氨酸根阴离子-四极相互作用的能量相当。在DNA-蛋白质界面上，芳环参与阴离子-四极相互作用的频率与盐桥中正电荷参与的频率相当，这表明在DNA-蛋白质（或膜-蛋白质）界面上阴离子-四极相互作用的作用没有得到充分认识。尽管在单链蛋白中不如盐桥那么频繁，